Iterated in vitro reproduction and genetic orphans

In an article soon to be published in the Journal of Medical Ethics, Rob Sparrow imagines a procedure via which multiple generations of human embryos might be created in the laboratory. Egg and sperm cells would first be generated from existing or new human pluripotent stem cell lines. The resulting eggs would be fertilised using the sperm to create zygotes and ultimately embryos. Embryonic stem cells would then be harvested from these embryos and used to create new egg and sperm cells, which would in turn be used to fertilise one another to create further embryos. This process could be iterated, in principle indefinitely.

Let’s call this procedure ‘iterated in vitro reproduction’ (Sparrow calls it ‘in vitro eugenics’). Iterated in vitro reproduction is not yet possible, but, citing recent developments in the science of stem cell-derived gametes, Sparrow argues that it may well become so, though he acknowledges are number of significant hurdles to its development. He also discusses a number of possible applications of the technology and calls for an ethical debate on these. The most controversial application would be in the creation of designer children. Consider the following case, which is a variant on one of the scenarios imagined by Sparrow:

Jack and Jill present to a fertility clinic. Jack provides a sperm sample, and fertility doctors harvest a number of eggs from Jill. These eggs are fertilized with Jack’s sperm to create embryos, from which embryonic stem cells are derived. These stem cells are then induced to develop into eggs or sperm which are used to fertilise one another, and so on. The process is iterated numerous times, and at each stage, the embryos are genetically screened via pre-implantation genetic diagnosis. This screening is used to inform a process of selective crossing, so that, over several generations, the population of embryos evolves towards certain genetic dispositions desired by Jack and Jill (a disposition towards longevity, say). This process is aided by adding small amounts of genetic material from stem cell lines derived from other individuals. Eventually, doctors identify an embryo with almost exactly the desired combination of genes, and this embryo is implanted into Jill’s womb and carried to term. A child, Jarvis, is born.

Cases like this raise numerous ethical issues, some of which are discussed by Sparrow and the seven commentators on his paper. However, they also raise an interesting conceptual question: would the users of such a technology be the genetic parents of the resulting offspring? Would Jack and Jill be the genetic parents of Jarvis?

Sparrows argues not. Though he does not himself discuss a case in which the resulting child’s genetic material comes predominantly from the couple who employ the technology, as in the case of Jack and Jill, it is clear what he would say about this case: even if Jarvis inherited approximately 50% of his DNA from each of Jack and Jill, Jack and Jill would not be his genetic parents. Given the intervening generations of embryos, Jack and Jill could at most be Jarvis’ genetic great-great-….grandparents (though they would of course also be his social parents). Jarvis would, in Sparrow’s terms, be a ‘genetic orphan’: an individual with no living genetic parents. (On this, see also an earlier paper by Sparrow.)

Interestingly, although a number of the commentators on Sparrow’s paper discuss the ethical implications of the claim that children like Jarvis would be genetic orphans, none question the claim itself. Yet I think there might be scope to question it. I think it could be argued that Jarvis is the genetic child of Jack and Jill.

What makes one individual the genetic parent of another? A initial, rough-and-ready definition might hold that P is the genetic parent of C if and only if

(a) C inherited some (or perhaps some specified proportion) of his or her genetic material from an egg or sperm derived from P, and

(b) the genetic material was not transmitted from the former to the latter via another individual.

The first condition serves to rule out cases in which the latter is not the genetic descendant of the former. The second serves to rule out cases in which the latter is the genetic descendent of the former, but not a direct descendant; the relation is one of genetic grandparenthood or some more indirect genetic relation, not one of genetic parenthood. (Obviously the notions of ‘inheritance’ and ‘transmission via’ would need to be further spelled out.)

Condition (a) is too restrictive, however. There are other species that reproduce asexually, without the creation of eggs or sperm, yet I would be inclined to say that there can still be genetic parenthood relations between the members of such species. Moreover, if it were possible for humans to reproduce without the creation of eggs and sperm, but in ways that nevertheless involved combining 50% of the genetic material from each member of a couple to produce an embryo, we would, I think, still be inclined to call the members of that couple the genetic parents of the child.  This suggests that we need to drop the reference to eggs and sperm in condition (a) and allow for other forms of genetic inheritance.

Condition (b) also requires modification. In every normal process of human reproduction, the parents pass genetic material to the resulting child via another ‘individual’ being, though not an individual human being: rather, they transmit genetic material via an individual eggs or sperm. Yet this would not lead us to conclude that, in normal reproduction, the reproducing individuals are really the genetic grandparents of the resulting child and it is the sperm or egg that is the parent. This suggests that we need to specify what kind of individual the intermediate descendant would need to be in order to break the genetic parenthood link. Plausibly, it would need to be a human being.

If we adopt the modifications suggested by these thoughts, then we might end up with something like the following account. P is the genetic parent of C if and only if

(a*) C inherited some (or perhaps some specified proportion) of its genetic material from P, and

(b*) the genetic material was not transmitted from the former to the latter via another human being.

Note, however, that on this definition, Jack and Jill may well qualify as the genetic parents of Jarvis. This is because it is not obvious that the intervening generations produced in the course of iterated in vitro reproduction that lead to Jarvis’ creation are generations of human beings. Some deny that zygotes and early human embryos qualify as human beings on the grounds that they lack the required intercellular integration. The embryo becomes a human being only when its component cells become integrated with and dependent on one another. Before then, the embryo is better thought of as simply a colony of human stem cells. On this view, early embryos are rather like gametes: they are not human beings themselves, they are rather intermediaries formed in the creation of one human being from others.

One attractive feature of this view can be seen by considering the case of monozygotic twins. Suppose Chris and Carol have monozygotic twins, Diana and Dahlia. Monozygotic twins are created by the splitting of one zygote (that is, a fertilized egg) or early embryo into two. That zygote/embryo goes out of existence when it splits to create the twins. Thus, it seems plausible to say that Chris and Carol transmit their genetic material to Diana and Dahlia via a zygote/embryo that is distinct from the two post-splitting zygotes from which they developed. Yet we would not want to say that this intermediary zygote was Diana and Dahlia’s genetic parent and Chris and Carol are the genetic grandparents. Rather, we would say that Chris and Carol are the genetic parents of the twins. The view that zygotes and early embryos are not human beings and the account of genetic parenthood that I offered above are together able to accommodate this: they allow us to maintain that the Chris and Carol are the genetic parents of the twins since the intervening individual is not a human being.

Likewise, if we accept these views, there is a case for concluding that iterated in vitro reproduction needn’t break ties of genetic parenthood. There is a case for concluding that Jack and Jill are the genetic parents of Jarvis, for Jarvis arguably inherited a proportion (perhaps almost 50%) of his genetic material from Jack and Jill, and the intervening generations of embryos were not generations of human beings.

 

 

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2 Responses to Iterated in vitro reproduction and genetic orphans

  • Heidi Mertes says:

    Would I be right to say that according to this definition, a clone has only one genetic parent, namely the person that was cloned, rather than two, namely the genetic parents of the cloned person? This would collide with many current conceptions of genetic parenthood: a paternity test would for instance argue against you. On the other hand, certainly when epigenetics are taken into account, much can be said for this view. However, it seems somewhat inconsistent to me. Consider the hypothetical case in which X and Y already have a child Z and want another child, but unfortunately have become infertile. Suppose they could clone their existing child Z, leading to child A. According to the definition provided, the genetic parent of A would be Z. On the other hand, if the genetic material of X and Y is repeatedly mixed but none of the in-between-embryos grows into a person, X and Y would remain the genetic parents. Moreover, if we would then decide to implant the same embryo of which the stem cell line to create the gamete was produced (don’t ask me why anyone would want to do this, but it is hypothetically possible if you make the stem cell line from a blastomere biopsy), X and Y would cease being the genetic parents again and hand over their title to the newborn… This then seems to be a definition that seeks out those who fulfill most of the criteria of being a genetic parent, a judgement that is subject to change when a better candidate comes along. This does not fit with our current conception of genetic parenthood.

    In 2008, I also undertook an attempt to define genetic parenthood in a way that would be most consistent with our ‘gut feelings’, but found it a nearly impossible task (DOI: http://dx.doi.org/10.1017/S096318010808002X). I do not think this is because we have not found the ‘right’ definition yet, but rather because genetic parenthood is a vague concept that is undefinable or at least debatable given all the new techniques of intervening in natural conception. For example the debate on mitochondrial replacement therapy illustrates this: whether or not the egg donor is a genetic parent of the resulting child is to a certain extent a useless debate (leaving the legal consequences aside), if you consider everyone that contributes genes a genetic parent, then yes, if you consider only those that contributed to the nuclear DNA, or only those that contributed DNA above a certain percentage a genetic parent, then no, but there is little sense in arguing that either vision would be right or wrong. We should be careful not to confuse semantics with normative issues. Maybe we should let go of the concept of genetic parenthood all together and just talk about genetic contributors (who come in different shapes and forms). Then we could go on to wonder in individual cases whether a certain genetic contributor can make a claim to any parental rights or is subjected to any parental obligations, but this will depend on much more than mere genetics.

    Anyway, I am looking forward to the special issue, it promises to be very interesting!

  • Tom Douglas says:

    Thanks for the comment Heidi, and also for the link to your paper, which I look forward to reading.

    On the cloning case, yes, my view could imply that the clone would have only one genetic parent, though this will depend on what proportion of C’s genetic material has to be inherited from P in order for P to be C’s genetic parent. If the proportion has to be approximately 50% then the clone would have no genetic parents. On that other hand, if, say, any significant proportion or any proportion near or greater than 50% is sufficient, then the clone would have one genetic parent (and in your example, Z would indeed be A’s genetic parent). I don’t find that counter-intuitive myself, but perhaps my intuitions about these cases are weird!

    I’m not sure I completely followed your last case, but I think you were pointing out that on my view, whether the individuals whose genes serve as inputs into the iterated IVR process count as the genetic parents of a resulting child will depend on whether any of the intervening embryos are allowed to develop to the point that they become human beings before stem cells are derived from them to produce gametes, and thus the next generation of embryos. If that’s right, then I agree, and I agree that’s a slightly weird implication of my view, although I’m still not convinced that I can see a better view: most of the obvious alternatives seem to me to yield very counterintuitive verdicts about monozygotic twins. But maybe I’ll be convinced otherwise when I read your paper!

    On the other hand, if you were imagining a case in which one of the intervening embryos was allowed to develop into a human being *after* stem cells had already been taken to create the next generation of embryos (suppose the embryo could survive the stem cell derivation process), then I don’t think that intervening embryo would become the genetic parent, because the transmission of genes occurred before that embryo became a human being. The individuals whose genetic material served as the inputs of the iterated IVR process would still be the most direct human being genetic predecessor of the child produced at the end of the IVR process.

    I think I agree that our everyday concept of genetic parenthood can probably not be captured in a set of necessary and sufficient conditions of the sort I was trying to develop. I also agree that it’s probably not normatively significant anyway. But perhaps there is some concept of ‘genetic contribution’ that comes in degrees and that is normatively significant, at least in the sense that prospective parents tend to care about it.

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